Surgery has always been a vital part of modern medicine to treat certain conditions that other interventional means cannot. However, surgical procedures are not without some significant complications, such as for example, hematomas, edema, and/or deep vein thrombosis.
Hematomas or blood collection outside the blood vessels can form at or near the surgical site as a result of trauma and migrate into a vital area (e.g., brain), which can lead to a life threatening condition (e.g., subdural hematoma, cephalhematoma, etc.). Edema or an abnormal accumulation of fluid beneath the skin, or in one or more body cavities can also occur during or after the surgery particularly when the surgery lasts a long period of time or when the patient is immobilized for long periods of time.
Deep vein thrombosis (DVT) can also be a significant surgical complication. A DVT is a condition in which a blood clot, or several blood clots, form inside a vein located deep within a muscle, typically in the lower part of the leg, the calf, though also possibly in other parts of the body such as, for example, an arm, a pelvis, spine, or a thigh. Sometimes, the blood clot breaks loose and travels through the bloodstream to the lungs and into the pulmonary arteries. Once in the pulmonary arteries the clots may create a blockage of the right ventricle, a relatively rare event, which is usually a fatal clinical condition, or may spread in the pulmonary smaller vessels, a rather more frequent event. This condition is generally referred to as “pulmonary embolism.” If not treated immediately, pulmonary embolism in many instances may have fatal consequences. Another complication may result from damage to the valves in the affected veins and consequently poor blood flow in the lower part of the leg. This condition, known as “post-thrombotic syndrome” is generally characterized by symptoms such as swelling, chronic pain and ulcers in the leg. These symptoms are usually associated as being long term symptoms of DVT.
One drug class that is known to the medical profession is the alpha adrenergic receptor agonists. In general, the alpha-adrenergic receptors mediate excitatory and inhibitory functions: alpha-1 adrenergic receptors are typically excitatory post-synaptic receptors, which generally mediate responses in the effector organ, while alpha-2 adrenergic receptors are located postsynaptically as well as presynaptically, where they inhibit release of neurotransmitters.
Examples of alpha adrenergic receptor agonists used clinically to treat different condition include clonidine, phenoxybenzamine and prazosin (for treatment of hypertension and opioid withdrawal), naphazoline (for nasal decongestion), UK-14,304 and p-aminoclonidine (for -glaucoma).
However, to date alpha adrenergic receptor agonists have not been widely appreciated as effective treatments for hematomas, edema or other fluid accumulation, and/or deep vein thrombosis. Thus, there is a need to develop alpha adrenergic receptor agonists to prevent, treat or reduce hematomas, edema or other fluid accumulation, and/or deep vein thrombosis.